DHX15 and Associated Diseases
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Backgrounds of DHX15 Gene
DHX15 is an adenosine triphosphate (ATP)-dependent RNA helicase that belongs to the DEAH-box (DHX) helicase family. DHX15, a member of the DEAH/H-box RNA helicase family, located in the cell nucleus that regulates pre-mRNA maturation, is involved in RNA metabolic processes, angiogenesis, blood cell maturation, and antiviral processes in vivo. It is also an essential intestinal defense member against external viruses and bacterial invasion. DHX15 is known to be involved in ribosome biogenesis by participating in some steps of small subunit maturation, as well as by segregating splicosome modules after it has completed its function. DHX15 is an RNA virus sensor that induces IFN-I and proinflammatory cytokines production in dendritic cells (DCs) by binding to double-stranded RNA (dsRNA) of RNA viruses in response to dsRNA and RNA viruses in vitro.
Functions of DHX15
DHX15 is a member of the RNA helicase family and plays an important role in multiple biological aspects.
- DHX15 participates in the innate immune response against viral infection by regulating multiple signaling pathways.
DHX15 regulates intestinal antiviral innate immunity by activating the Nlrp6-interferon pathway. Conversely, DHX15 directly associates with MAVS protein and activates nuclear factor kappa B (NF-kB) and mitogen-activated protein kinase (MAPK) pathways during antiviral responses.
- DHX15 involves in modulating pre-mRNA and pre-rRNA splicing.
- DHX15 plays a role in the further processing of RNA polymerase III primary transcripts by interacting with La (SSB) autoantigens.
DHX15 dedicates to tumorigenesis, both as a tumor-promoting factor in acute lymphoblastic leukemia, lung cancer, and prostate cancer, and as a tumor suppressor in glioma, hepatocellular carcinoma, and gastric cancer. DHX15 enhances the transcriptional activity of androgen receptor (AR) by stimulating Siah2-mediated ubiquitination, thereby promoting the progression of prostate cancer. In glioma, DHX15 is an antitumor gene, and it's Ia-Ib and III-IV motifs are important in its growth inhibitory function rather than its ATPase activity. Thus, DHX15 is a versatile protein involved in different stages of many types of cancer.
Fig.1 DHX15 is required to control RNA virus-induced intestinal inflammation. (Xing, 2021)
Different Expression of DHX15 in Diseases
Overexpression of wild-type DHX15 affected the expression levels of genes involved in splicing and ribosome biogenesis in HEK293T cells. The expression of DHX15 is down-regulated in glioma, and overexpression of DHX15 can inhibit the growth of glioma in vitro and in vivo. Knockdown of DHX15 inhibits the formation of homodimers or heterodimers of p65 and p50, resulting in reduced translocation into the nucleus, which in turn inhibits the transcription of target genes. DHX15 gene knockdown inhibits tumor growth and downregulated EBNA-1, EBER-1, and EBER-2 in vivo. Silencing the DHX15 gene could promote Burkitt lymphoma (BL) cell apoptosis, and inhibit cell proliferation in vitro and BL tumor growth in vivo, indicating that DHX15 might be a novel therapeutic target of the treatment for BL.
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Reference
- Xing, J.; et al. DHX15 is required to control RNA virus-induced intestinal inflammation. Cell reports. 2021, 35(12): 109205.
